A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential

被引:760
作者
Kögler, G
Sensken, S
Airey, JA
Trapp, T
Müschen, M
Feldhahn, N
Liedtke, S
Sorg, RV
Fischer, J
Rosenbaum, C
Greschat, S
Knipper, A
Bender, J
Degistirici, O
Gao, JZ
Caplan, AI
Colletti, E
Almeida-Porada, G
Müller, HW
Zanjani, E
Wernet, P
机构
[1] Univ Dusseldorf, Med Ctr, Sch Med, Inst Transplantat Diagnost & Cell Therapeut, D-40225 Dusseldorf, Germany
[2] Univ Nevada, Dept Pharmacol, Reno, NV 89523 USA
[3] Univ Dusseldorf, Sch Med, Dept Neurol, Mol Neurobiol Lab, D-40225 Dusseldorf, Germany
[4] Kourion Therapeut, D-40764 Langenfeld, Germany
[5] Case Western Reserve Univ, Skeletal Res Ctr, Cleveland, OH 44106 USA
[6] Univ Nevada, Vet Adm Med Ctr, Reno, NV 89557 USA
关键词
cord blood; regenerative medicine; ex vivo expansion; developmental potential;
D O I
10.1084/jem.20040440
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stern cells (USSCs) is described. This rare population grows adherently and can be expanded to 10(15) cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. Stereotactic implantation of USSCs into intact adult rat brain revealed that human Tau-positive cells persisted for up to 3 mo and showed migratory activity and a typical neuron-like morphology. In vivo differentiation of USSCs along mesodermal and endodermal pathways was demonstrated in animal models. Bony reconstitution was observed after transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs. Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep, resulted in up to 5% human hematopoietic engraftment. More than 20% albumin-producing human parenchymal hepatic cells with absence of cell fusion and substantial numbers of human cardiomyocytes in both atria and ventricles of the sheep heart were detected many months after USSC transplantation. No tumor formation was observed in any of these animals.
引用
收藏
页码:123 / 135
页数:13
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